Polyphenylsulfone (PPSU) plastic for baby bottles:an example for a comprehensive analytical NIAS assessment based on polymer-related

extractables and leachables.

Introduction

Since polycarbonate basically consisting of bisphenol A (BPA) was banned for the

production of baby bottles, the polyarylsulfone plastics polyethersulfone (PES) and

polyphenylsulfone (PPSU) became promising alternatives. PES and PPSU are

extremely resistant materials to chemical (acids/bases), mechanical and thermal

treatments. PES and PPSU are formally composed of bisphenol S (BPS) as well as

4,4‘-dihydroxybiphenyl (DHBP). Based on their bisphenolic molecular structure, both

substances might cause similar endocrine effects compared to the banned BPA.

In our study, we analyzed commercially available PES and PPSU materials used for baby

bottles. We focussed on the identification and quantification of polymer related

substances, mainly monomer derivatives as well as oligomers with a molecular weight

below 1.000 dalton, as potential migrants into baby food.

► PES and PPSU polymers from different manufacturers were characterized by 1H-NMR, size exclusion chromatography and

RP-HPLC analysis with respect to their end groups, their average molecular weight and their oligomer content < 1.000 dalton.

► PES and PPSU oligomers were identified by LC-ESI(+)-MS and (semi-) quantified based on the chromophore concentration

using the commercially available reference substance BPS at a specific UV-wavelength.

► Migration tests according to EU (VO) No. 10/2011 with food simulant for milk (50% EtOH) were performed. Neither SML values for

listed monomers nor TTC thresholds for not listed monomers and oligomers were exceeded.

► Based on our studies, baby bottles made from PES or PPSU materials can be evaluated as safe

alternatives for polycarbonate with regard to the migration of polymer related substances.

References Data published: Eckardt et al., 2018. Food Addit Contam Part A. DOI: 10.1080/19440049.2018.1449255

[1] Schaefer et al., 2004. DOI 10.1080/02652030310001637939[2] EFSA 2016. DOI: 10.2903/j.efsa.2016.4357

1H-NMR Average molecular weight & analysis of end groups HPLC-SEC Oligomers below 1.000 dalton

Conclusion

Martin Eckardt*, Annemarie Greb, Thomas Simat

Chair for Food Chemistry and Food and Skin Contact Materials, Technische Universität Dresden, Germany

* mail: martin.eckardt@chemie.tu-dresden.de

Polymer production and structures

𝑐𝑐: 𝐶ℎ𝑟𝑜𝑚𝑜𝑝ℎ𝑜𝑟𝑒 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 [µ𝑚𝑜𝑙 · 𝐿−1]𝑐𝑠: 𝑂𝑙𝑖𝑔𝑜𝑚𝑒𝑟 𝑐𝑜𝑛𝑐𝑒𝑛𝑡𝑟𝑎𝑡𝑖𝑜𝑛 [µ𝑔 · 𝐿−1]

Polyarylsulfones like PES and PPSU are usually prepared by

polycondensation of the chlorinated BPS derivative 4,4‘-dichloro-

diphenylsulfone (short Cl-BPS-Cl) with BPS (PES) or DHBP (PPSU)

in an aprotic polar solvent such as N-methylpyrrolidine (NMP) or

sulfolane.

By final addition of chloromethane, the hydroxyl end groups of the

linear polymer chains are partially methoxylated.

- 27th March 2018, ILSI Europe, Brussels, Belgium -

𝒄𝒄 = 𝒄𝒔 ·𝒏

𝑴𝒘Chromophore concentration

Po

ste

r o

nlin

e

12.9 13.1 12.812.1

13.7 14.2

16.7

14.6

21.5

0.4 0.4

2.2

0.5

6.4 7.2

0.4 0.4

2.1

PPSU-G

1

PPSU-F

1

PPSU-G

2

PPSU-F

2

PPSU-G

3

PPSU-F

3

PPSU-G

4

PPSU-F

4

PES-G

1

0

5

10

15

20

Avera

ge m

ole

cula

r w

eig

ht [k

Da]

Average molecular weight

0

5

10

15 Ratio of endgroups: -OMe/-ClE

nd

gro

up

ra

tio

: -O

Me

/-C

l

(A) (B)

Polymer structures of PES (A) and PPSU (B). PES exclusively consists of repeating units of BPS, whereas BPS and DHBP units alternate in the

PPSU polymer. Polymer end groups –R can be hydroxylated (–OH), chlorinated (–Cl) or methoxylated (–OMe).

► Total polymer characterization

1H-NMR (600 MHz) of completely dissolved PPSU polymers in CDCl3.

Determination of average molecular weight and ratio of endgroups (-OMe/-Cl).

Results of 1H-NMR analysis. Minor differences in average molecular weight, but big

differences in the ratio of methoxylated (-OMe) and chlorinated (-Cl) endgroups.

3.73.83.96.86.97.07.17.27.37.47.57.67.77.87.98.08.1ppm

PPSU: High -Cl content

PPSU High -OMe content

A

B

C

C

AB

► Identification and determination of linear and cyclic PES/PPSU oligomers after solvent extractionOligomer quantification: Chromophore concentration Extracts: Monomer derivatives and oligomers < 1.000 dalton

0 2 4 6 8 10 12 14 16 18 20 22 24

0

10

20

30

40

50

60

70

80

90

100

110

120

130

140

150

M4 M5M3M2

C3

D3

T1

D2

C7C6

C5

M1

UV

25

5 n

m [

mV

]

Retention time [min]

PES-G1C4

T2

Q1Q2

T3Monomer derivatives (M)

Oligomers (C/D/T/Q)

0 2 4 6 8 10 12 14 16 18 20 22 24

0

10

20

30

40

50

60

70

O12

O13

O11O7

O8

O6

O5

O2

O1M9M4

M7M3 M5

M8

UV

25

5 n

m [

mV

]

Retention time [min]

PPSU-G1

PPSU-G3

M6

Monomer derivatives (M)

Oligomers (O)

O9

O10

1000 Da cut

RP-HPLC chromatogram (UV 255 nm) of a milled PES material after

solvent extraction (conditions: acetonitrile, 1h, 120°C).

11 12 13 14 15 16 17 18 19 20 21

0

1

2

3

4

5

6

7

8

9

10

10 11 12 13 14 15 16 17 18 19 20 21 22 23

0

50

100

150

200

250

300

350

400

Inte

nsity 2

75 n

m [m

V]

Elution [mL]

Oligomer

< 1.000 Da

Oligomer

Polymer

Polymer

Inte

nsity 2

75

nm

[m

V]

Elution [mL]

PPSU-G3

PES-G1

Baseline

Size exclusion chromatography (HPLC-SEC) of completely dissolved polymers.

Estimation of relative oligomer content below 1.000 dalton.

0.50

0.47

0.56

0.510.47 0.47

0.38

0.46 0.47

PPSU PES

PPSU-G1 PPSU-F1 PPSU-G2 PPSU-F2 PPSU-G3 PPSU-F3 PPSU-G4 PPSU-F4 PES-G1

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

Olig

om

ers

belo

w <

1000 D

a [%

]

Relative oligomer content < 1.000 dalton determined by HPLC-SEC. Minor

differences between the polymers. Average oligomer content ~ 0.5 %.

RP-HPLC chromatograms (UV 255 nm) of two milled PPSU materials after

solvent extraction (conditions: acetonitrile, 1h, 120°C).

# Typ Struktur M

[g/mol]

ACN,

1h, 120°C [mg/kg]

EtOH

1h, 120°C [mg/kg]

50% EtOH

1h, 120°C [mg/kg]

M1 Monomer BPS 250.3 ~ 0.3 (NWG) ~ 0.3 (NWG) ~ 0.3 (NWG)

M2 Monomer BPS-OMe 264.3 2 1 0.5

M3 Monomer MeO-BPS-OMe 278.3 20 6 2

M4 Monomer Cl-BPS-OMe 282.7 111 48 14

M5 Monomer Cl-BPS-Cl 287.1 184 53 11

C3 Cyclic C[BPS]3 696.8 854 148 39

C4 Cyclic C[BPS]4 929.1 2483 357 52

C5 Cyclic C[BPS]5 1161.4 969 119 10

D1 Linear MeO-[BPS]2-OMe 510.8 n.A. n.A. n.A.

D2 Linear Cl-[BPS]2-OMe 515.0 122 36 8

D3 Linear Cl-[BPS]2-Cl 519.4 33 12 3

T1 Linear MeO-[BPS]3-OMe 742.8 149 36 8

T2 Linear Cl-[BPS]3-OMe 747.2 143 34 6

T3 Linear Cl-[BPS]3-Cl 751.7 n.A. n.A. n.A.

Q1 Linear MeO-[BPS]4-OMe 975.1 n.A. n.A. n.A.

Q2 Linear Cl-[BPS]4-OMe 979.5 n.A. n.A. n.A.

Table: Extraction results of milled PES-1 material after extraction with

different solvetns (ACN, EtOH, 50% EtOH, each 1h, 120°C).

# Typ Struktur M

[g/mol]

PPSU-G1

[mg/kg]

PPSU-G2

[mg/kg]

PPSU-G3

[mg/kg]

M6 Monomer DHBP 186.2 2 2 3

M3 Monomer MeO-BPS-OMe 278.3 n.A. 1 4

M7 Monomer DHBP-OMe 200.2 2 7 12

M4 Monomer Cl-BPS-OMe 282.7 10 14 70

M5 Monomer Cl-BPS-Cl 287.1 9 8 31

M8 Monomer MeO-DHBP-OMe 214.3 2 10 195

M9 Monomer Biphenyl 154.2 11 n.d. n.d.

O6 Cyclic C[BPS+DHBP]2 801.0 1241 1406 971

O1 Linear MeO-[BPS+DHBP]-OMe 446.5 16 94 42

O2 Linear Cl-[BPS+DHBP]-OMe 450.9 284 216 151

O5 Linear Cl-[BPS+DHBP+BPS]-Cl 687.6 712 245 11

O7 Linear MeO-[DHBP+BPS+DHBP]-OMe 614.7 62 485 639

O8 Linear MeO-[BPS+DHBP]2-OMe 846,9 31 204 70

O9 Linear Cl-[BPS+DHBP]2-OMe 851,4 397 281 187

O10 Linear Cl-[BPS+DHBP]2+BPS-Cl 1088.1 822 281 5

O11 Linear MeO-[DHBP+BPS]2+DHBP-OMe 1015.2 90 636 809

O13 Linear MeO-[DHBP+BPS]3+DHBP-OMe 1415.6 n.A. n.A. n.A.

Table: Total extraction of monomer derivatives and oligomers from three

different PPSU materials. Each 10 times consecutive acetonitrile, 1h, 120°C.

A) UV spectra of commercially available as well as self-synthesized chlorinated and methoxylated monomer derivatives of DHBP

and BPS. Almost equal molar absorbance (± 7%) of all derivatives at 255 nm. Usage of 255 nm as specific wavelength for

quantification of linear and cyclic PES/PPSU oligomers based on the chromophoric concentration as reported by SCHÄFER[1].

B) Linear calibration curves of all monomer derivatives of BPS and DHBP at the common wavelength of 255 nm. Usage of the

linear regression curve of the commercially available reference substance BPS for the quantification of PES/PPSU oligomers.

Cl-BPS-OMe (M4)

Cl-BPS-Cl (M5)

DHBP-OMe (M7)

MeO-DHBP-OMe (M8)

Cl-[BPS]2-OMe (D2)

Cl-BPS+DHBP-OMe (O2)

C

D

C) Structural examples of monomer derivatives (Mx) of BPS and DHBP with chlorinated,

methoxylated and hydroxylated end groups.

D) Structural examples of linear and cyclic PES (Dx) und PPSU oligomers (Ox).

C[BPS+DHBP]2 (O6)

y = 98.975x

y = 114.34x

0

2000

4000

6000

8000

10000

12000

14000

0 20 40 60 80 100 120

Are

a (

255

nm

) *

M [

mV

*min

*g/m

ol]

Concetration [mg/L]

BPS

DHBP

BPS-OMe

MeO-BPS-OMe

DHBP-OMe

MeO-BPS-Cl

Cl-BPS-Cl

MeO-DHBP-OMe

B

215 220 225 230 235 240 245 250 255 260 265 270 275 280 285 290 295 300

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

mola

r extinction [A

U*L

/mm

ol]

Wavelength [nm]

BPS (M1)

BPS-OMe (M2)

MeO-BPS-OMe (M3)

Cl-BPS-OMe (M4)

Cl-BPS-Cl (M5)

DHBP (M6)

DHBP-OMe (M7)

MeO-DHBP-OMe (M8)

equal absorbance

at 255 nmA

Specific migration limit (SML)

EU (VO) 10/2011 *

NIAS evaluation according to

Threshold of Toxicological Concern (TTC)

BPS (M1)50 µg/kg food simulant

Not listed monomers

10 µg/kg food simulant **Cl-BPS-Cl (M5) Linear oligomers

DHBP (M6) 6 mg/kg food simulant Cyclic oligomers

Results of migration tests according to EU (VO) 10/2011. 3 times consecutive migration into 50% EtOH (2h, 70°C).

Migration of monomer derivatives as well as oligomers from PPSU (A) and PES (B) bottles. (LOD: ~0.1 µg/kg).

► Migration into food simulants ► Risk assessment50% ethanol in water, 2h, 70°C, 3 times consecutive

𝑛 ∶ 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑎𝑟𝑜𝑚𝑎𝑡𝑖𝑐 𝑟𝑖𝑛𝑔𝑠 𝑖𝑛 𝑜𝑙𝑖𝑔𝑜𝑚𝑒𝑟 𝑠𝑡𝑟𝑢𝑐𝑡𝑢𝑟𝑒𝑀𝑤: 𝑀𝑜𝑙𝑒𝑐𝑢𝑙𝑎𝑟 𝑤𝑒𝑖𝑔ℎ𝑡 𝑜𝑓 𝑡ℎ𝑒 𝑜𝑙𝑖𝑔𝑜𝑚𝑒𝑟 [𝑔 · 𝑚𝑜𝑙−1]

PPSU-F3

DH

BP

DH

BP

-OM

e

Me

O-D

HB

P-O

Me

Me

O-B

PS

-OM

e

Cl-

BP

S-O

Me

Cl-

BP

S-C

l

O5

(L

ine

ar)

O6

(Z

yklis

ch

)

O7

(L

ine

ar)

DH

BP

DH

BP

-OM

e

Me

O-D

HB

P-O

Me

Me

O-B

PS

-OM

e

Cl-

BP

S-O

Me

Cl-

BP

S-C

l

O5

(L

ine

ar)

O6

(Z

yklis

ch

)

O7

(L

ine

ar)

PPSU-F2

0

1

2

3

4

5

6

7

8

9

10

0.08 0.19 0.08 0.170.52

0.110.43 0.27

0.60

7.42

2.281.87

0.630.21 0.28

Cramer III threshold

<L

OD

<L

OD

<L

OD

concentr

ation in food s

imula

nt [µ

g/k

g]

Migration 1

2 h, 70°C, 50 % EtOH,

Content per bottle: 300 mL

Migration 2

Migration 3

BP

S

Me

O-B

PS

-OM

e

Cl-B

PS

-OM

e

Cl-B

PS

-Cl

C4

PES-F1

0

1

2

3

4

5

6

7

8

9

10

2.10

3.98

0.93

1.52

concentr

ation in food s

imula

nt [µ

g/k

g]

<LO

D

A B

* Specific migration limit (SML). Evaluation of the third migration after three times

consecutive migration into food simulant for milk (50% ethanol, 2h, 70°C).

** Evaluation of not listed (10/2011) monomer derivatives of BPS and DHBP as well

as the linear and cyclic oligomers based on the TTC concept (TTC threshold for

Cramer III substances: 1.5 µg/kg bw & day).

Calculation of Cramer III threshold based on EFSA[2]: 3 kg baby bodyweight,

daily intake: 150 mL/kg bw Cramer III threshold: 10 µg/kg food simulant.

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blicati

on